Hospital-acquired infections linked to exposure to C.diff spores are a universal health-care crisis. Infection with C.diff is life-threatening to many patient populations, and contamination of equipment, materials, and surfaces with spores produced by C.diff bacteria occurs frequently, despite the best efforts at infection control. Part of the reason is that C.diff spores can survive on surfaces for long periods and are inherently difficult to destroy. Diligent efforts are necessary to eradicate the spores and require the use of disinfectant cleaning compositions with efficacy against spores and bacteria that produce them.
Similarly, in the pharmaceutical industry, manufacturing facilities have experienced a number of product recalls and plant shutdowns due to contamination with bacteria, viruses, fungi, spores (including spore-forming bacteria) and other biological contaminants. There has been an increase in the use of disinfectant sterilant products for cleaning pharmaceutical manufacturing equipment and surfaces.
The main products used in the cleaning and disinfection of surfaces contaminated with biological materials, specifically spores, are predominately oxidizing compositions, such as liquid or granular hypochlorite solutions (bleach), or hydrogen peroxide-based products such as EAST DEACON™ developed by Sandia National Laboratories. Specific to C.diff, the standard practice in most health care institutions is to use a product based upon sodium hypochlorite, also known as bleach. Hypochlorite-based disinfectants have been used with some success for surface disinfection in those patient-care areas where surveillance and epidemiology indicate ongoing transmission of C.diff. At present, there are no EPA-registered products with specific claims for inactivating C.diff spores, but there are a number of registered products that contain hypochlorite. As discussed below, while achieving efficacy in eradication of spores, use of currently available “bleach” products has many drawbacks.
Products used in the pharmaceutical manufacturing industry to eradicate spores and spore-forming bacteria rely on oxidizing chemistries, one of which is hydrogen peroxide. Like the use of hypochlorite-based products in health care institutions, the use of hydrogen peroxide chemistries for bacterial eradication in the pharmaceutical industry also suffers from many disadvantages.
Many sporicide products are available commercially. In addition to hypochlorite and hydrogen peroxide, products containing alcohols, peracetic acid (PAA), peracetic acid in combination with alcohols, hypochlorite or peroxide, and various products that utilize peroxygen sources and acetyl donors to generate both peracetic acid and hydrogen peroxide, are available as disinfectants or sterilants. These commercially available products have some disadvantages. Generally, alcohol-based disinfectants alone are not effective against C.diff or other spores, or spore-forming bacteria. In addition, many of these products have aesthetic and handling disadvantages, such as harshness (acidity or alkalinity), strong odor, and skin and mucous membrane irritation, due to high concentrations of active components. Most currently available products require overly cumbersome personal protective equipment to be used during their application to limit exposure, thus adding to their costs. The use, storage and transportation of these known, decontamination products thus present significant physical and health hazards and logistical challenges in shipping, handling and storage.
Hypochlorite bleach, although efficacious against C. diff, is not without these same disadvantages. Sodium hypochlorite has poor materials compatibility. Most sodium hypochlorite products are alkaline in nature and are corrosive to many materials, such as stainless steel, brass and copper. In addition, it has been shown that sodium hypochlorite can “strip away” waxes commonly used on hospital surfaces, making it an impractical choice for mopping applications. Further, sodium hypochlorite is associated with a difficult-to-rinse residue, which may contribute to its “stripping” effect. Finally, sodium hypochlorite demonstrates only moderate efficacy against certain organisms. It degrades rapidly in the presence of an organic soil load, thus negatively impacting its efficacy.
Oxidizing chemistries, such as bleach and hydrogen peroxide formulations, are known to be harsh chemistries requiring specific handling requirements. Depending on concentration, hydrogen peroxide may be subject to stringent handling restrictions. It may also be associated with strong odors and inhalation irritation issues. The OSHA permissible exposure limit (PEL) is 1 ppm for hydrogen peroxide. Some combination products, containing hydrogen peroxide as one component, may still be subject to air shipment restrictions based upon the concentration of hydrogen peroxide. In most cases, the products need to be shipped either by ground or sea causing delays in their arrival at required locations. Air shipment is possible for hydrogen peroxide, but quantities are severely limited and require special packaging.
Both sodium hypochlorite and hydrogen peroxide in high concentrations are corrosive, require special packaging, have limited transportation modalities and unstable without controlled transportation systems. Storage is also problematic. The storage of large amounts of highly corrosive and heat sensitive liquids is a safety issue. Bleach (hypochlorite) decomposes quickly at high temperatures resulting in a significant loss of efficacy and, therefore, has limited shelf life. Hydrogen peroxide spontaneously and irreversibly decomposes at elevated temperatures. Both hypochlorite- and hydrogen peroxide-based materials will also decompose rapidly when subjected to environmental contaminants such as dirt or blowing sand.
It is further noted that in addition to metal substrates, bleach and liquid hydrogen peroxide are incompatible with a number of non-metal substrates such as paints, soft metals, rubbers and plastics.
Finally, another disadvantage of most commercially available hydrogen peroxide and peracetic acid systems is that they cannot be sold as sterile. In order to create sterile products, the systems must be capable of being sterilized with gamma-irradiation. Gamma irradiation is commonly used in the pharmaceutical industry to sterilize cleaning compositions. Most commercial peracetic acid and hydrogen peroxide systems are not stable when exposed to gamma-irradiation and cannot be sterilized in this manner, requiring additional sterilization steps, if a sterile product is needed, adding to the costs associated with their use.
Accordingly, in the health care market and the pharmaceutical industry, an effective sporicide with EPA-approved claims against C.diff is needed to address the emerging health care and product contamination issues. C.diff spores can live on surfaces for years. C.diff spores are very difficult to kill. As mentioned above, sporicide products are available, but most have safety, odor, material compatibility and handling issues, among others. Currently, there are no EPA-approved products to address C.diff spores. The current practice in most health care institutions is to use a 10% solution of hypochlorite to clean all articles presumed to be contaminated with C.diff spores. There is a need, therefore, for a product having lower odor, better materials compatibility, improved safety profile, less stringent shipping requirements, and less onerous handling and storage parameters than currently existing products.
Formulations comprising peracetic acid, or components capable of generating peracetic acid (PAA) in situ, are effective sporicides and are nearly equivalent to acidified bleach, an industry standard for efficacy. A new sporicide system for each of the above-discussed markets (health care and pharmaceutical manufacturing) has been developed, having unexpected efficacy against spores and spore forming bacteria, such as C.diff, as well as other bacteria, virus, or fungi, but without the disadvantages of currently available products. Different embodiments of these inventive systems may be used depending on the needs of the market served; however, the foundation of the chemistry is the same: generation of peracetic acid through the perhydrolysis of tetraacetylethylene-diamine (TAED) using a specifically formulated hydrogen peroxide solution.
Product formulations containing peracetic and/or components for generating peracetic acid are known in the art. For example, systems comprising dry components exist that utilize solid peroxygen sources and acetyl donors, which, when mixed with water, produce peracetic acid (PAA). See e.g., U.S. Pat. No. 5,350,563, directed to a two-part perborate/acetyl donor powdered formulation. While dry product forms have application in certain cases, they are generally limited by slow generation of PAA at room temperature, and, therefore, there is a preference for more rapid acting liquid products in certain applications. Use of dry peroxygen components is disadvantageous due to the time needed to generate hydrogen peroxide before activation (combination) with the acetyl donor. A particular disadvantage to multi-component dry systems is that the components dissolve very slowly in water, such that the desired concentration of active ingredients is not fully available until later stages. There is also an additional risk that undissolved components will remain and not be rinsed away. On the other hand, a system or formulation utilizing a liquid hydrogen peroxide component has been found to generate PAA much faster as the perhydroxyl ion is available immediately upon combination with an acetyl donor, regardless of whether the acetyl donor is in solid or liquid form.
Other liquid commercial products containing both peracetic acid and hydrogen peroxide are also known. For example, a liquid product produced by Decon Labs, known as “SPORGON” comprises 7.35% hydrogen peroxide and 0.23% peracetic acid; however, the high level of hydrogen peroxide in use requires a limitation of exposure. OSHA limits personal hydrogen peroxide exposure to 1 ppm. In addition, the product requires at least three hours to achieve sterilization. Another example is OXONIA ACTIVE, an acidic liquid sanitizer, produced by Ecolab. This product is highly corrosive and has a hydrogen peroxide level of 27.5% and peracetic acid level of 5.8%. The high level of hydrogen peroxide requires, in addition to exposure limits, stringent shipping and handling requirements. In most instances, these products cannot be gamma-irradiated, the preferred method for sterilization of pharmaceutical industry disinfectants.
Liquid systems for generating PAA are also known. By way of example, U.S. Pat. Nos. 6,514,509 and 7,235,252 are directed to systems for preparing organic peroxy acids using a parent solution and activator and requiring a hydroalcoholic environment (at least 10% alcohol) with an acid pH. The alcohol purportedly acts as an additional germicide. In contrast, the present invention does not utilize or require a hydroalcoholic environment and does not utilize strong inorganic acids to maintain an acid pH. Importantly, peracetic acid is generated in an alkaline environment, not acidic, and the resulting product rapidly converts to a neutral pH upon peracetic acid generation. There is no need for an additional germicide.
European Patent 0 598 170 B1 is a cleaning composition based on hydrogen peroxide (or a peroxygen source) combined with acetyl triethyl citrate as a bleach activator. The bleach activator requires emulsification with at least two surfactants having different HLB values. The components are all combined in one unitary liquid composition.
The present invention is based upon combining an acetyl donor, alkalinity agents and a liquid hydrogen peroxide source to produce an effective concentration of peracetic acid in situ to destroy C.diff spores. The present invention is a ready-to-use system upon activation (combination of ingredients) and requires no further dilution or manipulation of components. Generation of peracetic acid is much faster due to the immediate availability of the perhydroxyl ion, as compared to products using a dry peroxygen source. Surprisingly, the present formulations are effective at much lower concentrations of peracetic acid than currently available products.
The present invention provides sporicidal formulations having a pH in the neutral range (4-8), which allows for easier disposal versus highly alkaline or acidic products, and has superior materials compatibility against soft metals, plastics, resins and other materials, as compared to bleach. The inventive formulations also result in low odor products that are less caustic or irritating to personnel than existing products, including those containing higher levels of peracetic acid, and may eliminate the need for respiratory protection required for application of higher concentrations of PAA and acidified bleach. They have no detectable levels of acetic acid or hydrogen peroxide. Most commercially available PAA-containing products require the use of acetic acid to stabilize the peracetic acid for longer shelf life, greatly increasing the odor profile. Since peracetic acid is generated in situ with the present invention, there is no need for the addition of acetic acid or any other acid, thus reducing or eliminating the odor profile.
Unexpectedly, the formulations of the present invention are efficacious against a wide range of bacteria, viruses, fungi and spores, including C.diff, without the addition of additional biocides or germicides and, hence, are less costly. Microbial efficacy has been shown even in the presence of an organic soil load and at a lower concentration of peracetic acid. Surfactants utilized in the present system are excellent cleaners, improving efficacy in the presence of an organic soil. Finally, the inventive formulations comprise low levels of hydrogen peroxide, which is not subject to stringent shipping and handling requirements.
Tetraacetylethylenediamine (TAED) is the preferred acetyl donor for the present invention. A formulated solution of hydrogen peroxide is the chosen perhydroxyl source. Both TAED and hydrogen peroxide are currently registered EPA-active ingredients. While several different embodiments exist for the inventive formulations, they all share the advantageous properties of preparation at a neutral pH, low odor, better materials compatibility, improved safety profile and high efficacy.
The present invention contemplates two different embodiments: one, a two-part system consisting of a dry TAED powder activator and a liquid formulated hydrogen peroxide solution, and the other, a three-part system consisting of a 2-component liquid TAED activator (comprising a TAED suspension and an alkaline liquid solution) and the same liquid formulated hydrogen peroxide as used in the two-part system. Both systems, upon activation (combination), generate lower levels of peracetic acid with unexpected microbial efficacy.
It is an object of this invention to provide a low odor disinfectant having efficacy against bacteria, viruses, fungi and other biological materials, including spores and spore-forming bacteria, such as C. diff. 
It is a further object of this invention to provide a low-odor peracetic acid solution with greatly improved safety and handling features over currently available products.
Still a further object of this invention is to provide a system for rapid generation of peracetic acid in an alkaline pH environment, which quickly drops into the neutral range upon peracetic acid generation, resulting in a product that is usable within a short period of time after combination and having a use life of at least 24 hours.
Yet a further object of this invention is to provide a peracetic acid solution which has efficacy even in the presence of an organic soil load.
It is a further object of this invention to provide an effective, safer alternative to hypochlorite or other oxidizing chemistries for use in health care environments to eradicate C. diff spores.
These and other objects of the invention will be apparent based upon the description herein.